Racial Differences in Donor-Derived Cell-Free DNA and Mitochondrial DNA After Heart Transplantation, on Behalf of the GRAfT Investigators

Shah, P; Agbor-Enoh, S; Lee, S; Andargie, TE; Sinha, SS; Kong, H; Henry, L; Park, W; McNair, E; Tchoukina, I; Shah, KB; Najjar, SS; Hsu, S; Rodrigo, ME; Jang, MK; Marboe, C; Berry, GJ; Valantine, HA; GRAfT Investigators

doi:10.1161/circheartfailure.123.011160

Heart failure & cardiomyopathies

Racial Differences in Donor-Derived Cell-Free DNA and Mitochondrial DNA After Heart Transplantation, on Behalf of the GRAfT Investigators

Circ Heart FailPublished 20 Feb 2024Prospective cohort study

Main finding · Primary composite outcomeResultHazard ratio 2.61 95% CI 1.35–5.04

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Authors' conclusion

Elevated dd-cfDNA and cell-free mitochondrial DNA after heart transplant may mechanistically be implicated in the higher incidence of AR and worse clinical outcomes in Black transplant recipients.

Study context

Population: Heart transplant recipients (GRAfT cohort)
Participants: 148 recipients

Exposure: Black vs White heart transplant recipients
Blackn = 65
Whiten = 83reference
Outcome: Composite of:
Acute rejection (AR)
Graft dysfunction (LVEF <50% and decrease by ≥10%)
Death
Follow-up: 1 and 2 years

Methodological detailsmulticentre, longitudinal

Multicentre
Longitudinal

Main finding

Primary composite outcome

Hazard ratio

2.61

95% CI 1.35–5.04

P = 0.004

By group

Black

1 year: 43%
2 years: 55%

White

1 year: 23%
2 years: 27%

1 year

Black43%

White23%

2 years

Black55%

White27%

Blackvs White

HR 2.61 (95% CI 1.35–5.04); P = 0.004

As reported in the abstract

%donor-derived cell-free DNA (dd-cfDNA) associated with primary composite outcome: multivariable HR 1.15 (95% CI 1.03-1.28, P=0.010)

Observational data: associations, not effects.

Further findings

AR incidence

P = 0.002

Black43%

White19%

Antibody-mediated rejection prevalence

P < 0.001

Black20%

White2%

Cell-free mitochondrial DNA

P < 0.001

Black185 788 copies/mLIQR 101 252-422 133

White133 841 copies/mLIQR 75 346-337 990

Outcome	Black	White	P value
dd-cfDNA after transplant	0.09% (IQR 0.001–0.30)	0.05% (IQR 0.001–0.23)	P = 0.003

dd-cfDNA after transplant

Beyond 6 months, persistent rise in dd-cfDNA with higher levels in Black patients

Original publication

Racial Differences in Donor-Derived Cell-Free DNA and Mitochondrial DNA After Heart Transplantation, on Behalf of the GRAfT Investigators. Circ Heart Fail. Published 20 February 2024. doi:10.1161/circheartfailure.123.011160

Read the original article ↗

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